Lately I’ve been doing more digging into my genetic results from 23andme in search of an answer to that nagging question in the back of my mind…
Why do I have endometriosis?
I’ve always struggled with the fact that there is no known cause. This is, after all a big part of finding a solution… right?
This is a big reason why I find the genetic aspect so interesting. As I dig deeper into my personal code, I am piecing together a clearer understanding of why my body carries endometriosis.
Sulfation & Estrogen Metabolism
I listened to an interesting talk by Dr. Amy Yasko that helped me further piece together my genetic breakdowns in relation to estrogen metabolism.
She provided information on a key component to this: the sulfation process.
Turns out that the sulfation process is the main pathway for estrogen metabolism, which is believed to be involved in the inactivation of estrogens.
Sulfation regulates how much of these active estrogens are in your tissues. This includes the breakdown of estradiol, a highly active growth promoting hormone that stimulates endometriosis.
Your Liver & Estrogen Metabolism
Your liver is your primary site for sulfation, where synthesis and transformation of these estrogens takes place. To help visualize how this all goes down, I found a helpful diagram of the estrogen metabolism process here.
As you can see, the following genes are involved in the estrogen metabolism process:
- SULTs (Sulfotransferases)
- CYP (Cytochromes)
- COMT (Catechol-O-methyltransferase)
Enzymes of the same name (SULT, CYP & COMP) encode these genes and carry out their roles along the way.
I have breakdowns in all three of these areas with two heterozygous mutations with SULT1A1 & one homozygous mutation with SULT2A1.
I have nine heterozygous mutations with my CYP gene variations and one homozygous breakdown. I also have two homozygous mutations with COMT.
Hence, my body has a lot of bumps along the way to breaking down estrogen and releasing it correctly out of my body.
The Role of Estrogen Sulfates
The process by which estrogens are released from your ovaries, and then transported to target tissues, is not fully understood, but an increasing body of scientific data believes that sulfation and desulfation of estrogen plays an important role.
SULTs (Sulfotransferases) are responsible for estrone and estradiol sulfation. Highest SULT activity happens in your liver.
In addition to your liver, estrogen SULT activity has also been found in a variety of tissues including those in your breasts, uterus, adrenal glands and small intestines. Estrogen SULT activity has also been found in the placenta.
Studies have suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers.
Wonder if the same would be true of endometrial implants? Seems this should be a key area of research.
What I gather from all of this is the cause and effect of my genetic breakdowns, assuming I have less enzymes to deactivate harmful estrogen from my tissues.
On the Positive Side?
I’ve been a bit overwhelmed by the data that I received from my 23andme testing. But I think that I’m slowly piecing things together.
While I don’t have a concrete solution to all this at this point, I’m starting to wrap my head around some of the biochemistry involved. I’m even able to comprehend the genetic articles in the scientific journals I come across, Lol.
I find it empowering to research and find these connections. Perhaps by sharing my personal discoveries I can help other endo sisters out there with similar genetic breakdowns.
Maybe together we can figure out our own “cause”.
There is a great company that I recently learned about called Juneau Biosciences who is doing a wide scale genetic study on endometriosis to see if they can detect patterns and trends.
Wonder if they’ve found any connections with SULT, CYP and COMT?
Have you done genetic testing? Do you have issues with SULT, CYP or COMT?
I’d love to hear from you.
Much Love,
Excellent article. You are further along the pathway of deciphering all this. I am consulting someone next week to help me interpret my results and guide me through addressing issues. I have various mutations that indicate problems breaking down estrogen and also issues with estrogen receptor genes. I discovered this via Nutrahacker.
I took DIM for about 6 weeks last Sept but stopped on instruction from my naturopath due to dizzy spells. DIM can reduce sodium. I then experienced the best 8 weeks I’ve had in a long time with 2 relatively pain free periods and plenty of energy. This didn’t last as the effects of DIM would have worn off. I now think it was wrong to stop DIM and instead the reduced sodium should have been addressed. I’m convinced that the DIM (diindolymethane) helped eliminate estrogen from my body. I intend to start taking it again with the help of my new nutritionist.
Thanks CB. I have issues with my estrogen receptors too! ESR1 – Estrogen receptor alpha. Good ‘ol nutrahacker 🙂 I’m not sure exactly what that means yet. I haven’t tried DIM. Interesting that it reduces sodium.
When I had my hair tested I showed that I had low sodium and potassium levels which points to adrenal issues (which I am pretty sure I have). Also relates back to lithium. Dr. Yasko talks about this in the video I included at the top of this post.
I learned that my body has likely been low on lithium for who knows how long since I have mutations with MTR and SHMT and low magnesium levels, which plays into all of it too.
Long story short, I’m a hot mess, Lol. Good for you for seeking out help. It’s all very overwhelming on your own. Good luck!
I’m a hot mess too! I can’t recall where I saw the info about DIM and its possible effect on sodium. Here’s an overview of DIM but bear in mind it’s quite conservative http://www.thefreshcarrot.ca/ns/DisplayMonograph.asp?StoreID=5020E137E9014BC38944489AF1F99926&DocID=bottomline-diindolylmethane I think the best approach is to monitor when taking to see if any of the possible side effects occurs. Also may affect blood sugar levels.
When it comes to endo, the drugs offered come with many possible side effects and risks. DIM seems innocuous to me in comparison if used correctly. I am aware that it should not be taken constantly.
Looking forward to reading more of your fascinating discoveries.
Hi Aubree and CB,
I have Endometriosis and have just learnt I hold following Comt mutation Cyp, dbh, Drd all homozygous.
It’s all new to me and I don’t know of any websites to look up learn more on this estrogen metabolism gene, any suggestion?
I have just commenced dim or indole 3 as known.
If you know of any oestrogen clearing supplements or dietary be appreciated.
Anyone have low progesterone as a result of poor oestrogen metabolism?
Cheers
KA
Hi KA –
Did you do testing though 23andme.com? If so, then the web site nutrahacker.com is awesome for supplementation recommendations. But it can all be overwhelming. Would surely be helpful if you found a naturopath or functional doctor to help decipher it all 🙂
Nutrahacker recommended hydroxyB12 for COMT mutations. B12 plays a BIG role in the methylation cycle. I blogged about this in the past: http://peacewithendo.com/2015/01/could-it-be-vitamin-b12-deficiency.html
Before starting on B12 Dr. Yasko recommends testing your Lithium levels. Lithium plays a role in B12 transport. Without it, then B12 supplementation is washed out. Recommend checking out Dr. Yasko’s web site. Her focus is on Autism, but she gets into the methylation cycle, which is key: http://www.dramyyasko.com/resources/autism-pathways-to-recovery/chapter-6/
For CYP Nutrahacker recommends DIM. Another option to try would be Calcium-D-Glucarate, which helps break down estrogen. I have not tried either option.
Also recommended for CYP is NAC (n-acetyl cysteine). I am leery of taking this, however, since I have breakdowns with CBS, which relates to sulphur levels. NAC is a sulphur compound. That being said, a lot of ladies with endometriosis have had success by supplementing with NAC.
I have progesterone issues but think that I also have low estrogen levels. I spent a decade on birth control pills, which I believe has had a big impact on my natural hormone levels.
Best of luck. It’s always nice to connect with others trying to figure this all out 🙂
It’s been very interesting to read this article! I have been thinking about taking a DNA test with 23 and me! My husband, too since he was adopted. Doctors haven’t been much help and I also participated in the End to Endo study. I have been dying to know their findings!
Hi Nicole –
I’m curious to hear what they found too. I did ask about the genes mentioned in this article and they said there was no correlation on a large scale with endo, though that doesn’t mean it’s not the case with me. It’s all so individual – getting to know your code is so interesting! Would love to hear what you find out about yours.
Much LOVE,
Aubree.
Aubree great article . Suggest further research in to cytokines and interleukins . Elevated levels related to endo and in men low sperm count or no sperm count at all abd possibly later the risk of prostate cancer . High levels induce inflammotary receptors in endo nodules especially in women who have not had excision surgery. However to lower both cytokines and IL 8 drinking green tea as well as eating green mung has been shown to lower these . Also the use of Essential therapuetic oils as well as bio identical hormones all help flare ups too. Watching your diet eating healthy avoiding synthetic hormones wherever possible , balancing stress levels all help .
Also bear in mind that even progesterone dependent or estrogen dependent can give you the same results .
Its all in the genetics .
Hi Fae –
Thanks for the suggestions.
Much LOVE,
Aubree.
Hello Aubree,
I, like yourself have been deciphering mine and my Autistic Son’s 23andme results for the past year. And like yourself I feel like I am slowly piecing the puzzle together. I just recently came across a very interesting article.
In relation to your statement in a previous post above:
“There is a great company that I recently learned about called Juneau Biosciences who is doing a wide scale genetic study on endometriosis to see if they can detect patterns and trends. Wonder if they’ve found any connections with SULT, CYP and COMT?”
I have a double mutation(+/+) in the SULT2A1. I found that this mutation can cause high phenols in the body and slows the detox of estrogens (because they use the same pathway for clearance) and can cause endometriosis! This may be a piece of your puzzle.
THIS IS THE ARTICLE:
Phenol compounds
Phenols come from plants and bacteria. Some phenols like resveratrol and green tea catechins are have enormous health benefits. But because of their similar shape, these and other phenol compounds compete with estrogen and adrenalin/dopamine for metabolism through the COMT pathway; therefore if the imbalanced gut is causing more phenols to leak into the body, it will slow the clearance of estrogen and stress hormones. This increase of adrenalin/noradrenalin will cause more pressure on the COMT and MAO systems, two pathways that are genetically slowed in many people.
So if the gut is producing a lot of phenols (during SIBO or other gut infections) then the body cannot detox stress hormones and estrogens very well. The reasons is that the phenols sit in the same parking space in the COMT enzyme as does adrenalin, dopamine, and estrogen.
High phenol levels from the gut can lead to pain, anxiety, insomnia, fatigue, low thyroid, fibroids, endometriosis, weight gain and more just by interfering with the COMT pathway and putting excess pressure on the MAO system. But that is not all that gut-derived phenols can do.
Phenols are also metabolized through the sulfation pathway and they can lower sulfate levels. The SULT1A1 and SULT1A2 genes are responsible for taking a toxin, neurotransmitter, bile acid or hormone and gluing it to a molecule of sulfate. This is the sulfate transfer that is so important to Phase II detox. All phenols whether they come from the gut or the diet are processed through the SULT pathway. When phenols are metabolized this way they remove sulfate from the body. And sulfate is often lacking in people with imbalanced methylation and chronic disease.
Individuals with SULT SNPs have a SLOWED sulfation pathway already, and when phenols from the gut enter the body in high amounts it slow down their phase II sulfation even more. In this way lots of phenol production from the gut bacteria can greatly impair your detox system increasing sensitivity to smells, foods, chemicals and more. The phenol connection to methylation is the idea behind the Feingold Diet for the treatment of Autism and other neurological and developmental issues.
The full article can be found here:
http://www.beyondmthfr.com/the-gut-origin-of-methylation-problems/
ANOTHER ARTICLE STATES:
http://scdlifestyle.com/2010/04/phenols-and-salicylates-what-they-are-and-why-it-matters/
“Phenols are nothing more than natural chemicals made up of a benzene ring with one or more hydroxyl (OH) groups attached to it (science talk for how it is put together). They are found in many of the foods we eat like fruits, veggies, and nuts and can also be man-made for use in common non-food applications such as toothpaste, hair dyes, medicine, and disinfectants. It is important to remember that most foods have some level of phenols in them (there are many subgroups, compounds, and close chemical relatives) and that they are natural and can even be beneficial to the body, as is the case with antioxidants in fruit.”
After I pondered this article for a few hours, I remembered I had purchased and tried a product called “No-Fenol by Houston Enzymes” for my Autistic son. This product contains the enzyme Xylanase that helps breakdown Phenols (the cell wall of most fruits and veggies) in your body! At the time I purchased it, I did not have our 23andme results. (My Son’s Nutrahacker report shows he is hetererozygous +/- for the SULT2A1) I only purchased it because I had read several articles that people with Autism sometime have problems breaking down Phenols in their diet. He currently only takes a digestive enzyme with every meal. So…… I new that the No-Fenol had the Xylanase Enzyme that breaks down phenols in the diet. I searched the internet for foods with Phenols and Oh my…….I eat most of the food on that list! Also you can see from the article, high Phenols in the gut can also cause endometriosis!! I don’t currently have endo but at one time in my early 20’s because of my terrible menstrual cramps, my Dr. thought I may. I was going to be tested for it but I soon found out I was pregnant and never did.
I recently began taking 1 No-Fenol capsule with each meal and I have had such good response. My brain fog has lifted and my mood and well being is much better. I believe the No-Fenol is now breaking down the phenols in my diet so there is no “bottle neck” and the Estrogens are now able to clear more efficiently since they both use the same pathway for clearance.
I have tried DIM several times in the past because also have several CYP mutations and 2 double mutations in the ESR2 gene (also causes Estrogen metabolism problems) that the Nutrahacker supplement suggestion was DIM. I did not feel good taking the DIM and now I know why! DIM is Broccoli and other cruciferous vegetables that are high in Phenols! I plan to continue with the No-Fenol a few more days and try the DIM again with it soon.
I believe that having your 23andme Genetic Test run($199) and then ordering the Nutrahacker report ($50) is the best way to be you and your families best advocate for their health. Nutrahacker gives supplement suggestions for your specific genetic mutations.
I thought I would share this information with you and your readers. I hope this information helps others as it has me. Live Blessed!
This is very interesting. Thank you so much for sharing. Phenols have not been on my radar, but I wonder if this is why I have issues with green tea.
I also recently started supplementing with Pine Bark (Pycnogenol) since I’ve heard such good things about it helping with endometriosis. But I think that my body reacted negatively to it.
I’m wondering now if that’s because of the high phenols?
Thanks for bringing this to my attention and adding another piece to the puzzle 🙂
NAC is supposed to be great for several reasons, but be careful if trying it, because it causes stomach problems for a % of people.
I just had my 23andme results ran through geneticgenie.com and found out I am homozygous in CBS 699T and heterozygous in MTHFR 677T (also homo in VDR Bsm and heterozygous in quite a few others). I’m so confused by all of this. I have extremely low D3 (like 10, 50 is normal) and also high estrogen. Could these gene mutations be causing that? I read you need to treat CBS before MTHFR, but HOW? Add to all of this I contracted borrelia on the 4th of July (relapsing fever, possibly Lyme disease, still can’t find a single doctor to really tell me because even with 2 positive test results I was told they were false positives because “there isn’t any Lyme here”) (the Lyme groups are who encouraged me to do the genetic testing, which seems to have opened up a whole new can of worms). Any help relating the high estrogen and low D3 to the CBS or MTHFR gene mutations, and any help on how to treat the CBS mutation would be greatly appreciated!!! Thanks so much! I wish you all good health soon!!! 😀
Hi Kris. I can relate to your overwhelm. Haha. I’d recommend seeking out a functional doctor who can help you sort things out. Have you read the book Medical Medium? Highly recommend this one. It helped me get to the bottom of most of the issues I have, which he relates back to the Epstein Barr Virus: http://peacewithendo.com/2016/11/epstein-barr-virus-ebv-blame.html
Vitamin D3 is a big deal, especially with your immune system. I have issues with my VDR gene. Given this, the presence of advanced EBV and a decade on birth control pills all lends the way to endo and the pain in my body today. Here’s more on Vit D: http://peacewithendo.com/2017/02/low-vitamin-d-endometriosis.html
Interesting article. I have some Homozygous SULT and CYP snps and I am heterozygous for some COMT snps. I also had cervical cancer at a young age, yet have none of the HPV strains that caused cancer. What my doc at the time suspected is that my Mother took a big pharma drug called Diethylstilbestrol (DES) will pregnant with me. It was given to women in the 40s, 50s and 60s to prevent miscarriages. I was the 4th child after 5 miscarriages. My Mother denies taking it, but the evidence in my body proves otherwise. I found a drug bank site out of Canada that showed the enzymatic actions of the drug. It affected our Neurotransmitters and our ability to detox. I’ve also found other research where is showed early thymus atrophy (that is where our natural killer cells of our immune system are made) and when the drug was sent to the FDA for approval, it was already shown to cause cancer in young women and pituitary tumors in rats. They suspect 10M women were exposed to the hazardous drug that is now classified as an endotoxin. These epigenetic changes can also be passed on to future generations. With 10M women exposed, that multiplier number has the potential to be HUGE! It makes me wonder if this exposure flipped many of our genetic switches and is contributing to the growing infertility problem in the world today.
Interesting. Thanks for sharing.
Promote hydroxylation (Hydroxocobalamin, Lugol’s) which will help with cleaning out bad estrogens. Hydroxylation addresses CYP mutations.
Increase progesterone (my wife uses bio identical progesterone lozenges).
This has helped many people who have suffered with endometriosis fully recover.
Hi! I just found this looking for connections between endo and COMT mutations (I am homozygous for both of the COMT mutations that impair estrogen metabolism also). I thought that menopause would finally be the end of pain for me and now, about 1 year since a period, the pain is back. It is awful because every time it comes back when I haven’t had it in a while I start worrying if it’s something new/else/worse. (Met/Met, you know, we worry). Anyway, I need to check these other genes for additional mutations and I want to thank you for laying it out so clearly here. peace!
I recently finished reading Liver Rescue by Anthony William and he explains more about methylation and genetic factors. He says the results that come back on the genetic tests that show mutation is really because of a sluggish liver. Everything goes back to your liver. Since finding Anthony William and his Medical Medium books I’ve shifted focus from so much of the genetic factor to addressing viral factors like EBV. I highly recommend checking out Liver Rescue: https://amzn.to/2Fkoosm
OMG the more I read the more you are blowing my mind. I also have immune issues — any respiratory virus my body completely over-reacts and makes me a mucous factory, which when I was a kid caused >30 pneumonias, now it doesn’t tend to get that bad. It all started when I was 4 and got a bad case of chicken pox, and i’ve been looking into the EBV thing too. Seems like some viral infections trigger this “epigenetic” thing and BAM!!!
Yes! Glad you’re seeing the connections, love. EBV has been a huge part of my story too. I think I was born with it, that’s where the “genetic” factor really comes into play with the viruses, heavy metals, DDT, etc.